Although most tissues of Metazoa are comprised of cells electrotonically coupled to each other by low resistance (gap) junctions, and these have been studied for almost thirty years, the understanding of the way in which cells control these junctions under physiological conditions is still very incomplete. It seems clear that the major obstacle has been the lack of preparation of two coupled cells where extensive control and testing of both intracellular and extracellular media can be achieved. To improve our knowledge in these areas we propose to use and experimental preparation of two naturally isolated coupled cells where extensive testing can be performed. This preparation is the lateral axons from the crayfish nerve cord, where the junctional channels can be studied with a variety of techniques. Furthermore, as the axons allow from the application of internal perfusion techniques, the intracellular medium can be controlled and numerous natural compounds relevant to the physiological functions of these channels can be tested. The objectives of the present series of studies are: 1. to study the cellular mechanisms that seem to regulate gap junctional channels under physiological conditions, and; 2. to determine the influence that humoral factors might have on the cellular mechanisms that control gap junctional channels.